This Mentored Patient-Oriented Research Career Development Award (K23) will enable Dr. Simeonova to pursue her long-term career goal of becoming an independent patient-oriented investigator with focus on longitudinal high-risk research in early-onset bipolar disorder. Dr. Simeonova's short-term goal for the duration of the award is to concentrate on the following areas of training and research: 1) developmental psychopathology and psychobiology; 2) longitudinal high-risk research with focus on determinants of resilience in infants and toddlers of mothers with bipolar disorder; and 3) translational science. Many children with familial genetic risk for bipolar disorder are exposed to multiple risk factors, but follow normative and resilient developmental trajectories and do not experience psychopathology. Currently, very limited knowledge exists on resilience, the dynamic developmental process by which positive adaptation is achieved in the context of adversity, in this vulnerable population. Understanding mechanisms and pathways contributing to and promoting resilient trajectories in high-risk offspring of mothers with bipolar disorder is of critical importance for the development of novel, effective, evidence-based prevention and early intervention approaches. Consistent with the priorities of the National Institute of Mental Health and to address this need, Dr. Simeonova's training will be accomplished via: 1) meetings, guided readings, and tutorials with mentor W. Edward Craighead, Ph.D., co-mentor Zachary Stowe, M.D., and an expert team of internal and external consultants; 2) formal course work in developmental psychopathology and psychobiology, translational social neuroscience, and other relevant training and research areas; 3) supervised hands-on experience in the collection and analysis of data using a multilevel perspective and a diverse set of approaches to study longitudinally the early social-emotional development of offspring of mothers with bipolar disorder; 4) training in design and methods used in longitudinal research and advanced statistical techniques for modeling of neurodevelopmental trajectories; 5) training in the assessment and analysis of dyadic social-emotional behavior and interactions; 6) training in the responsible and ethical conduct of research with women and pediatric populations; and 7) attendance of national and international conferences, journal clubs, and other relevant training and research activities. The research plan, informed by a developmental psychopathology framework, will concentrate on the following aims: 1) characterization of the early developmental trajectory of infants and toddlers of mothers with bipolar disorder with a focus on social-emotional development; 2) identification of early factors contributing to resilience in young high-risk offspring of mothers with bipolar disorder; 3) characterization of the oxytocinergic system as related to mother-infant social interactions in young high-risk offspring and their mothers with bipolar disorder. This work is innovative, because it aims to expand knowledge in this vulnerable population based on resilience models. The proposed integrated training and research programs, together with the strong research environment at Emory University, will complement Dr. Simeonova's background in clinical science and place her in a position to conduct independent integrative high-risk research on social-emotional and neurodevelopmental factors in the etiology of early-onset bipolar disorder. PUBLIC HEALTH RELEVANCE: Many high-risk children of parents with bipolar disorder are exposed to multiple risk factors, but follow normative and resilient developmental trajectories and do not experience psychopathology. Currently, very limited knowledge exists on resilience, the dynamic developmental process by which positive adaptation is achieved in the context of adversity, in this vulnerable population. Understanding mechanisms and pathways contributing to and promoting resilient trajectories in young high-risk offspring is of critical importance for the development of novel prevention and early intervention approaches.